CD80

Official Full Name

CD80 molecule

Organism

Homo sapiens

GeneID

941

Background

The protein encoded by this gene is a membrane receptor that is activated by the binding of CD28 or CTLA-4. The activated protein induces T-cell proliferation and cytokine production. This protein can act as a receptor for adenovirus subgroup B and may play a role in lupus neuropathy. [provided by RefSeq, Aug 2011]

Synonyms

B7; BB1; B7-1; B7.1; LAB7; CD28LG; CD28LG1;

Bio Chemical Class

mRNA target

Protein Sequence

MGHTRRQGTSPSKCPYLNFFQLLVLAGLSHFCSGVIHVTKEVKEVATLSCGHNVSVEELAQTRIYWQKEKKMVLTMMSGDMNIWPEYKNRTIFDITNNLSIVILALRPSDEGTYECVVLKYEKDAFKREHLAEVTLSVKADFPTPSISDFEIPTSNIRRIICSTSGGFPEPHLSWLENGEELNAINTTVSQDPETELYAVSSKLDFNMTTNHSFMCLIKYGHLRVNQTFNWNTTKQEHFPDNLLPSWAITLISVNGIFVICCLTYCFAPRCRERRRNERLRRESVRPV

Open

Approved Drug

1 +

Clinical Trial Drug

5 +

Discontinued Drug

1 +

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Detailed Information

CD80 is a key immune co-stimulatory molecule involved in the activation of T cells and the regulation of immune responses. Being a member of the immunoglobulin superfamily, CD80's role goes beyond only activating T cells; it also controls the equilibrium between immunological tolerance and immune response via interactions with other immune components. The fundamental second signal needed for T cell activation comes from CD80 binding to CD28. Several signaling pathways—including NF-κB, MAPK, and PI3K/Akt—which control T cell proliferation, cytokine output, and other purposes are triggered by this contact.

Structure and Function of the CD80 Gene

Encoded by the CD80 gene, the protein is a membrane receptor that mostly generates immunological co-stimulating signals by connecting to the CD28 receptor on T cells, therefore encouraging T cell proliferation and cytokine release. By interacting with immune inhibitory receptors such as CTLA-4 and PD-L1, CD80 also modulates the strength and duration of immunological responses. More especially, CD80 improves the contact between T cells and antigen-presenting cells (APCs), therefore enabling immunological responses. In addition, CD80 can serve as a receptor for adenovirus group B, participating in the viral infection process. Moreover, CD80 is involved in the interaction between T cells and B cells, hence producing antibodies and immunological memory.

Role of CD80 in Immune Responses

In immunological responses, CD80 provides the second signal to boost T cell responses to MHC-antigen complexes. Two signals are needed for T cell activation: the interaction of CD28 with CD80/CD86 generates the second signal; the first signal is given by MHC antigens bound to T cell receptors (TCR). By activating the NF-κB and MAPK signaling pathways, the binding of CD80 to CD28 stimulates T cell proliferation and cytokine generation. Apart from encouraging T cell activation, CD80 binds to CTLA-4 to aid in reducing too strong immunological activation during the latter phases of T cell activation, hence preserving immune tolerance.

In T cell activation as well as in controlling immunological tolerance, CD80 is very vital. CD80 reduces the activation of T cells by interacting with CTLA-4, therefore limiting the immune system from targeting self-tissues when T cells are too active. The control of autoimmune illnesses depends much on this ability.

CD80 in Autoimmune Diseases

CD80 plays an important role in various autoimmune diseases. Upregulation of CD80 has been shown to be tightly linked in studies to the onset of disorders like rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic lupus erythematosus (SLE). In these disorders, CD80 increases too strong T cell activation, hence boosting the immune system's assault on self-tissues and causing immunological dysregulation. For this reason, CD80 is now a possible target for treating many disorders.

In systemic lupus erythematosus, for instance, CD80 stimulates T cell activation, hence aggravating immune response overactivity and injury to self-tissues. In multiple sclerosis, the binding of CD80 to CD28 helps pathogenic T cells to proliferate, hence enhancing the immunological assault on the neurological system. Thus, in immune modulation treatments, focusing on CD80 has shown promise in the treatment of certain disorders.

CD80 in Tumor Immunity

The function of CD80 in tumor immunity is multifarious and complicated. Through its interaction with CD28, CD80 increases T cell activation, therefore strengthening the immune system's response to tumors and enabling the overcoming of tumor immune evasion. Conversely, tumor cells may upregulate CD80 expression, hence fostering immunological tolerance and so stifling anti-tumor immune responses. Therefore, CD80 may boost anti-tumor T cell activity as well as cause immunological tolerance to lower tumor immunity.

Studies on tumor immunity have shown that co-stimulatory actions of CD80 and CD86 are quite important. Effective expression of CD80/CD86 may activate T cell subsets, hence inducing immunological rejection of tumor cells. On the other hand, tumor cells devoid of CD80 and CD86 lack immunogenicity and cannot set off a strong immune response. Because of its function in tumor immunity, CD80 has so gained great interest as a target for immunotherapy.

Figure 1 illustrates the co-stimulatory pathway of CD80/86 in immune cell activation. Figure 1. Co-stimulatory pathway of CD80/86.

Applications of CD80 in Immunotherapy

As immunotherapy develops quickly, CD80 has attracted a lot of attention as a possible immune-modulating target. Numerous CD80-based treatment approaches are under investigation right now. For treating autoimmune illnesses including rheumatoid arthritis and kidney transplants, for instance, the CD80/CD86 fusion protein Belatacept has been authorized. Moreover, combo treatments including immune checkpoint inhibitors and CD80 show great possibilities. Combining CD80 with PD-1/PD-L1 inhibitors has been shown in studies to be able to overcome the restrictions of single-agent treatments and raise immune response rates in cancer patients.

In tumor immunotherapy, interactions with molecules like PD-L1 may promote immunological tolerance and boost immune rejection, thereby transcending the function of CD80 in controlling T-cell activation. Thus, developing CD80-related immunotherapy techniques, in conjunction with other immunotherapies including as checkpoint inhibitors and cancer vaccines, has the potential to provide fresh advancements in cancer immunotherapy.

References:

Chaudhri A, Xiao Y, Klee AN, et al. PD-L1 Binds to B7-1 Only In Cis on the Same Cell Surface. Cancer Immunol Res. 2018 Aug;6(8):921-929.
Ford ML, Adams AB, Pearson TC. Targeting co-stimulatory pathways: transplantation and autoimmunity. Nat Rev Nephrol. 2014;10(1):14-24.

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